Anticancer combination therapy

Abstract

The invention describes anti-cancer therapies comprising using a 3G-EGFR inhibitor and an anti-IGF antibody, each as described herein.

1 . A method of treating and/or preventing an oncological or hyperproliferative disease, comprising administering to a patient in need thereof a therapeutically effective amount of a 3G-EGFR inhibitor selected from the group consisting of compound 1 and compound 2—or a pharmaceutically acceptable salt thereof— 
       
         
           
           
               
               
           
         
         and an anti-IGF antibody, wherein said antibody molecule has heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:1 (CDR1), SEQ ID NO:2 (CDR2) and SEQ ID NO:3 (CDR3) and has light chain CDRs comprising the amino acid sequences of SEQ ID NO:4 (CDR1), SEQ ID NO:5 (CDR2) and SEQ ID NO:6 (CDR3). 
       
     
     
         2 . The method according to  claim 1 , wherein the 3G-EGFR inhibitor is administered simultaneously, concurrently, sequentially, successively, alternately or separately with the anti-IGF antibody. 
     
     
         3 . A method of treating and/or preventing an oncological disease, the method comprising administering to a patient in need thereof an anti-IGF antibody, having heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:1 (CDR1), SEQ ID NO:2 (CDR2) and SEQ ID NO:3 (CDR3) and having light chain CDRs comprising the amino acid sequences of SEQ ID NO:4 (CDR1), SEQ ID NO:5 (CDR2) and SEQ ID NO:6 (CDR3), in combination with a 3G-EGFR inhibitor selected from the group consisting of compound 1 and compound 2—or a pharmaceutically acceptable salt thereof 
       
         
           
           
               
               
           
         
       
     
     
         4 . The method according to  claim 3 , wherein the anti-IGF antibody is administered simultaneously, concurrently, sequentially, successively, alternately or separately with the 3G-EGFR inhibitor. 
     
     
         5 . A pharmaceutical composition comprising a 3G-EGFR inhibitor selected from the group consisting of compound 1 and compound 2—or a pharmaceutically acceptable salt thereof— 
       
         
           
           
               
               
           
         
         an anti-IGF antibody, wherein said antibody molecule has heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:1 (CDR1), SEQ ID NO:2 (CDR2) and SEQ ID NO:3 (CDR3) and has light chain CDRs comprising the amino acid sequences of SEQ ID NO:4 (CDR1), SEQ ID NO:5 (CDR2) and SEQ ID NO:6 (CDR3), and, optionally, one or more pharmaceutically acceptable carriers, excipients and/or vehicles. 
       
     
     
         6 . A kit comprising a first pharmaceutical composition comprising a 3G-EGFR inhibitor selected from the group consisting of compound 1 and compound 2—or a pharmaceutically acceptable salt thereof— 
       
         
           
           
               
               
           
         
         and optionally one or more pharmaceutically acceptable carriers, excipients and/or vehicles; and 
         a second pharmaceutical composition comprising an anti-IGF antibody, wherein said antibody molecule has heavy chain CDRs comprising the amino acid sequences of SEQ ID NO:1 (CDR1), SEQ ID NO:2 (CDR2) and SEQ ID NO:3 (CDR3) and has light chain CDRs comprising the amino acid sequences of SEQ ID NO:4 (CDR1), SEQ ID NO:5 (CDR2) and SEQ ID NO:6 (CDR3), and, optionally, one or more pharmaceutically acceptable carriers, excipients and/or vehicles. 
       
     
     
         7 . The method according to  claim 1 , wherein the 3G-EGFR inhibitor is compound 1. 
     
     
         8 . The method according to  claim 1 , wherein the antibody molecule has a variable heavy chain comprising the amino acid sequence of SEQ ID NO:7 and a variable light chain comprising the amino acid sequence of SEQ ID NO:8. 
     
     
         9 . The method according to  claim 1 , wherein the antibody molecule has a heavy chain comprising the amino acid sequence of SEQ ID NO:9, and a light chain comprising the amino acid of SEQ ID NO:10. 
     
     
         10 . The method according to  claim 1 , wherein the oncological disease to be treated is cancer harboring one or more EGFR mutation. 
     
     
         11 . The method according to  claim 10 , wherein at least one EGFR mutation is selected from Del19 (deletion in exon 19), L858R and T790M. 
     
     
         12 . The method according to  claim 11 , wherein the at least one EGFR mutation is Del19. 
     
     
         13 . The method according to  claim 11 , wherein the at least one EGFR mutation is L858R. 
     
     
         14 . The method according to  claim 11 , wherein the at least one EGFR mutation is T790M. 
     
     
         15 . The method according to  claim 11 , wherein the cancer harbors at least two EGFR mutations selected from the group consisting of Del19/T790M and L858R/T790M. 
     
     
         16 . The method according to  claim 10 , wherein the cancer is non-small cell lung cancer (NSCLC).